Total knee replacement is the most common total joint procedure in the United States, and the number of procedures has grown dramatically over the past two decades to over the 580,000 per year. Despite the general success of cemented total knee replacement, aseptic loosening requiring a revision surgery is still common, particularly for younger and more active patients. New pilot data obtained from cemented tibial tray components following in vivo service show that there is extensive resorption of trabecular bone that interlocks with cement under the tibial tray and that this resorption may occur within the first few years following implantation. The working hypothesis is there is an early loss of mechanical micro-interlock between the cement and bone following implantation and this results in a loss of functional strength of the tibial tray component. In clinical practice, loss of interlck could cause an increased risk of component migration and aseptic loosening, particularly for high demand patients. The goal of this research program is to achieve arthroplasties that function successfully for the lifetime of the patient without the need for revision. In this competitive renewal the applicants leverage the experience gained from the current funding cycle on fixation of total hip replacement following in vivo service and combine these with new approaches to assess and address loosening issues associated with knee replacements. The specific aims are to (1) discover the temporal and spatial changes to the fixation morphology following in vivo service with particular attention to short term in vivo service; (2) determine th influence of these morphological changes on the structure/mechanical function relationship for the fixation interfaces and complete tibial tray constructs; (3) explore potential mechanical mechanisms responsible for trabecular bone resorption from interdigitated cement-bone regions; (4) determine the loss of functional strength of whole constructs due to in vivo service; and (5) perform translational biomechanics studies to mitigate bone loss through improved load transfer to the underside of the tibial tray (termed a type A scenario) using targeted design changes. If trabecular bone loss under tray cannot be prevented (termed a type B scenario), determine amount of distal fixation needed to prevent loosening for 'normal' and 'high demand' patients. A synergistic combination of experimental and computational methods is used to address these aims.